Abstract
OBJECTIVES: This randomized, placebo-controlled pilot trial evaluated the efficacy and safety of abatacept in patients with anti-synthetase syndrome-associated interstitial lung disease (ASyS-ILD). METHODS: Participants with active ASyS-ILD were randomized to receive abatacept (n = 9) or placebo (n = 11) for 24 weeks, followed by a 24-week open-label extension with abatacept for all participants. The primary endpoint was a change in % predicted forced vital capacity (%FVC) from baseline to week 24. Secondary endpoints included changes in the FVC (ml), % predicted diffusing capacity of the lung for carbon monoxide (%DLCO), shortness of breath questionnaire (SOBQ) and pulmonary disease activity on a visual analogue scale (VAS) at weeks 24 and 48. Pre-post baseline analysis of FVC and quantitative image analysis (QIA) of high-resolution computed tomographic scans were performed. Data were analysed using a generalized linear mixed model. The study was not powered for primary or secondary endpoints. RESULTS: At week 24, there was no significant difference in the primary endpoint of %FVC change between abatacept and placebo (between treatment difference of -0.35, 95%CI -6.91 to 6.21, P = 0.914) and in all secondary endpoints. However, by week 48, trends favouring abatacept in %FVC, FVC (ml), %DLCO and SOBQ were observed without statistical significance. There was a significant improvement in pulmonary disease activity VAS and pre-post baseline slopes of %FVC and QIA scores in the abatacept arm. Abatacept was generally well tolerated. CONCLUSION: Abatacept did not significantly improve %FVC at 24 weeks. However, trends at 48 weeks suggest potential benefits, supporting the need for a larger, long-term randomized controlled trial. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; NCT03215927.